10-Propargyl-10-Deazaaminopterin in Treating Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma or Hodgkin's Lymphoma

• Sponsor: Spectrum Pharmaceuticals, Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00052442
• Collaborator: National Cancer Institute (NCI) (NIH), Memorial Sloan Kettering Cancer Center (Other)
• Enrollment: 72
• Location: 1
• Arms: 5
• Duration (Months): 79
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of 10-propargyl-10-deazaaminopterin in treating patients who have recurrent or refractory non-Hodgkin's lymphoma or Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: pralatrexate	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

• Determine the efficacy of 10-propargyl-10-deazaaminopterin, in terms of objective response rate, duration of response, and time to disease progression, in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma or Hodgkin's lymphoma.

• Determine the impact of pharmacokinetics on toxicity and drug elimination in patients treated with this drug.

• Determine the toxicity of this drug in these patients.

• Determine the effect of prior chemotherapy response duration on duration of response in patients treated with this drug.

• Correlate, if possible, the pharmacodynamics (area under the curve) of this drug with tumor response and toxicity (mucositis) in these patients.

• Correlate, if possible, intraerythrocytic folate or homocysteine levels with severity of mucositis in patients treated with this drug.

• Determine whether levels of the RFC-1 folate transporter, folylpolyglutamate synthetase, and folylpolyglutamate hydrolase are markers of response in patients treated with this drug.

OUTLINE: This is an open-label study.

Patients receive 10-propargyl-10-deazaaminopterin IV over 1 hour on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) may receive 2 additional courses beyond the CR.

PROJECTED ACCRUAL: A total of 39-72 patients (12-35 for cohort 1 and 17-37 for cohort 2) will be accrued for this study within 10-36 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of 10-Propargyl-10-Deazaaminopterin (PDX) in Relapsed or Refractory Aggressive Non-Hodgkin's Lymphomas and Hodgkin's Disease
• Study Start Date: Aug 1, 2002
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 135 mg/m^2 Pralatrexate 1/2 weeks Pralatrexate (PDX) 135 mg/m^2 administered as an intravenous (IV) infusion over one hour into a side arm of a running intravenous infusion of normal saline for 1/2 weeks.	Drug: pralatrexate; Other Names: Folotyn 10-Propargyl-10-Deazaaminopterin (PDX)
Experimental: 30 mg/m^2 Pralatrexate 3/4 weeks PDX 30 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 3/4 weeks.	Drug: pralatrexate; Other Names: Folotyn 10-Propargyl-10-Deazaaminopterin (PDX)
Experimental: 30 mg/m^2 Pralatrexate 6/7 weeks PDX 30 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 6/7 weeks.	Drug: pralatrexate; Other Names: Folotyn 10-Propargyl-10-Deazaaminopterin (PDX)
Experimental: 45 mg/m^2 Pralatrexate 6/7 weeks PDX 45 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 6/7 weeks.	Drug: pralatrexate; Other Names: Folotyn 10-Propargyl-10-Deazaaminopterin (PDX)
Experimental: 270 mg/m^2 Pralatrexate 2/4 weeks PDX (270 mg/m^2) administered as an IV bolus over 3-5 minutes into a side arm of a running intravenous infusion of normal saline for 2/4 weeks.	Drug: pralatrexate; Other Names: Folotyn 10-Propargyl-10-Deazaaminopterin (PDX)

Outcome Measures

Primary Outcome Measures

1. Response Rate [3 weeks]

   Per Response Evaluation Criteria in T-cell and B-cell Lymphoma for target lesions and assessed using computerized tomography (CT) and or Positron emission tomography CT (PET CT) by local investigators: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=50% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Secondary Outcome Measures

1. Toxicities of Pralatrexate [3 weeks]

   Adverse events; number of patients with at least one adverse events reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed Hodgkin's lymphoma or, using the World Health Organization (WHO) classification, aggressive non-Hodgkin's lymphoma including:

• Large B- or T-cell lymphomas (including transformed lymphomas)

• Mantle cell lymphoma

• Immunoblastic lymphoma

• At least 1 unidimensionally measurable lesion

• At least 2 centimeter (cm) by conventional techniques OR

• At least 1 cm by spiral computerized tomography (CT) scan

• Lymph nodes no greater than 1 cm in the short axis are considered normal

• Relapsed or refractory disease after first-line chemotherapy

• Cohort 1:

• No more than 3 prior conventional cytotoxic chemotherapy regimens

• Must have had at least a partial response (PR) lasting no more than 6 months or refractory disease

• Patients with disease refractory to or relapsed less than 100 days from peripheral blood stem cell (PBSC) transplantation are not eligible

• Cohort 2:

• No limit on prior treatment

• Must have had at least a PR to the last therapy lasting at least 6 months

• Patients who have received high-dose chemotherapy as part of peripheral blood stem cells (PBSC) transplantation are eligible if relapse occurred at least 100 days after transplantation

• No clinically significant pleural effusions or ascites

• No active brain or leptomeningeal metastases

• Treated Central nervous system (CNS) disease allowed

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count greater than 1,000/mm^3

• Platelet count greater than 75,000/mm^3

• Hemoglobin at least 10 g/dL

Hepatic

• Bilirubin less than 1.5 times upper limit of normal (ULN)

• Aspartate aminotransferase/alanine aminotransferase (AST/ALT) no greater than 2.5 times ULN (4 times ULN if liver involvement)

• Alkaline phosphatase no greater than 5 times ULN

Renal

• Creatinine no greater than 1.5 mg/dL OR

• Creatinine clearance at least 50 mL/min

Cardiovascular

• No symptomatic congestive heart failure

• No New York Heart Association class III or IV heart disease

• No unstable angina pectoris

• No cardiac arrhythmia

• No myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months

• No history of orthostatic hypotension

• No ECG evidence of acute ischemia or significant conduction abnormality (e.g., bifascicular block or 2nd or 3rd degree atrioventricular blocks)

• No uncontrolled hypertension requiring active manipulation of antihypertensive medications

• No grade III or IV edema

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No ongoing or active infection

• Febrile episodes up to 38.5° Celsius without signs of active infection allowed

• No other concurrent active cancer

• No other concurrent serious medical illness

• No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

• At least 3 months since prior monoclonal antibody therapy (e.g., rituximab)

Chemotherapy

• See Disease Characterisitics

• At least 4 weeks since prior cytotoxic chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered

Endocrine therapy

• At least 7 days since prior steroids

• No concurrent steroids

Radiotherapy

• See Disease Characteristics

• At least 4 weeks since prior radiotherapy and recovered

Surgery

• More than 4 weeks since prior major surgery

Other

• No prior antifolates

• No concurrent folic acid supplementation

• No other concurrent investigational agents

• No concurrent combination antiretroviral therapy for human immunodeficiency virus (HIV)-positive patients

• No other concurrent investigational or commercial agents or therapies with the intent to treat the malignancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021

Sponsors and Collaborators

• Spectrum Pharmaceuticals, Inc
• National Cancer Institute (NCI)
• Memorial Sloan Kettering Cancer Center

Investigators

• Study Chair: Owen A. O'Connor, MD, PhD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Spectrum Pharmaceuticals, Inc
• ClinicalTrials.gov Identifier: NCT00052442
• Other Study ID Numbers: CDR0000258425; MSKCC-02078; NCI-H02-0100
• First Posted: Jan 27, 2003
• Last Update Posted: Aug 25, 2021
• Last Verified: Aug 1, 2021

• Keywords provided by Spectrum Pharmaceuticals, Inc: recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult Burkitt lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent mantle cell lymphoma; recurrent adult Hodgkin lymphoma; recurrent grade 3 follicular lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; 10-deazaaminopterin

Study Results

Participant Flow

Arm/Group Title	135 mg/m^2 Pralatrexate 1/2 Weeks	30 mg/m^2 Pralatrexate 3/4 Weeks	30 mg/m^2 Pralatrexate 6/7 Weeks	45 mg/m^2 Pralatrexate 6/7 Weeks	270 mg/m^2 Pralatrexate 2/4 Weeks
Arm/Group Description	Pralatrexate 135 mg/m^2 administered as an IV infusion over one hour into a side arm of a running intravenous infusion of normal saline for 1/2 weeks.	Pralatrexate 30 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 3/4 weeks.	Pralatrexate 30 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 6/7 weeks.	Pralatrexate 45 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 6/7 weeks.	Pralatrexate 270 mg/m^2 administered as an IV bolus over 3-5 minutes into a side arm of a running intravenous infusion of normal saline for 2/4 weeks.
Period Title: Overall Study
STARTED	16	3	27	11	15
COMPLETED	16	3	27	11	15
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	135 mg/m2 Pralatrexate 1/2 Weeks	30 mg/m2 Pralatrexate 3/4 Weeks	30 mg/m2 Pralatrexate 6/7 Weeks	45 mg/m2 Pralatrexate 6/7 Weeks	270 mg/m2 Pralatrexate 2/4 Weeks	Total
Arm/Group Description	Pralatrexate 135 mg/m^2 administered as an IV infusion over one hour into a side arm of a running intravenous infusion of normal saline for 1/2 weeks.	Pralatrexate 30 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 3/4 weeks.	Pralatrexate 30 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 6/7 weeks.	Pralatrexate 45 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 6/7 weeks.	Pralatrexate 270 mg/m^2 administered as an IV bolus over 3-5 minutes into a side arm of a running intravenous infusion of normal saline for 2/4 weeks.	Total of all reporting groups
Overall Participants	16	3	27	11	15	72
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.3 (16.1)	54.3 (14.4)	55.7 (16.5)	52.7 (11.4)	57.1 (15.1)	54.1 (15.2)
Sex: Female, Male (Count of Participants)
Female	4 25%	2 66.7%	10 37%	7 63.6%	5 33.3%	28 38.9%
Male	12 75%	1 33.3%	17 63%	4 36.4%	10 66.7%	44 61.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	1 6.3%	1 33.3%	2 7.4%	2 18.2%	0 0%	6 8.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	2 12.5%	1 33.3%	3 11.1%	2 18.2%	3 20%	11 15.3%
White	10 62.5%	0 0%	21 77.8%	5 45.5%	9 60%	45 62.5%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	3 18.8%	1 33.3%	1 3.7%	2 18.2%	3 20%	10 13.9%

Outcome Measures

1. Primary Outcome

Title	Response Rate
Description	Per Response Evaluation Criteria in T-cell and B-cell Lymphoma for target lesions and assessed using computerized tomography (CT) and or Positron emission tomography CT (PET CT) by local investigators: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=50% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	3 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	135 mg/m^2 Pralatrexate 1/2 Weeks	30 mg/m^2 Pralatrexate 3/4 Weeks	30 mg/m^2 Pralatrexate 6/7 Weeks	45 mg/m^2 Pralatrexate 6/7 Weeks	270 mg/m^2 Pralatrexate 2/4 Weeks
Arm/Group Description	Pralatrexate 135 mg/m^2 administered as an IV infusion over one hour into a side arm of a running intravenous infusion of normal saline for 1/2 weeks.	Pralatrexate 30 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 3/4 weeks.	Pralatrexate 30 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 6/7 weeks.	Pralatrexate 45 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 6/7 weeks.	Pralatrexate 270 mg/m^2 administered as an IV bolus over 3-5 minutes into a side arm of a running intravenous infusion of normal saline for 2/4 weeks.
Measure Participants	16	3	27	11	15
Count of Participants [Participants]	15 93.8%	3 100%	27 100%	11 100%	15 100%

2. Secondary Outcome

Title	Toxicities of Pralatrexate
Description	Adverse events; number of patients with at least one adverse events reported.
Time Frame	3 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	135 mg/m^2 Pralatrexate 1/2 Weeks	30 mg/m^2 Pralatrexate 3/4 Weeks	30 mg/m^2 Pralatrexate 6/7 Weeks	45 mg/m^2 Pralatrexate 6/7 Weeks	270 mg/m^2 Pralatrexate 2/4 Weeks
Arm/Group Description	Pralatrexate 135 mg/m^2 administered as an IV infusion over one hour into a side arm of a running intravenous infusion of normal saline for 1/2 weeks.	Pralatrexate 30 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 3/4 weeks.	Pralatrexate 30 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 6/7 weeks.	Pralatrexate 45 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 6/7 weeks.	Pralatrexate 270 mg/m^2 administered as an IV bolus over 3-5 minutes into a side arm of a running intravenous infusion of normal saline for 2/4 weeks.
Measure Participants	16	3	27	11	15
Count of Participants [Participants]	16 100%	3 100%	27 100%	11 100%	15 100%

Adverse Events

Arm/Group Title	135 mg/m^2 Pralatrexate 1/2 Weeks		30 mg/m^2 Pralatrexate 3/4 Weeks		30 mg/m^2 Pralatrexate 6/7 Weeks		45 mg/m^2 Pralatrexate 6/7 Weeks		270 mg/m^2 Pralatrexate 2/4 Weeks
Arm/Group Description	Pralatrexate 135 mg/m^2 administered as an IV infusion over one hour into a side arm of a running intravenous infusion of normal saline for 1/2 weeks.		Pralatrexate 30 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 3/4 weeks.		Pralatrexate 30 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 6/7 weeks.		Pralatrexate 45 mg/m^2 administered as an IV infusion over 15 minutes into a side arm of a running intravenous infusion of normal saline for 6/7 weeks.		Pralatrexate 270 mg/m^2 administered as an IV bolus over 3-5 minutes into a side arm of a running intravenous infusion of normal saline for 2/4 weeks.
All Cause Mortality
	135 mg/m^2 Pralatrexate 1/2 Weeks		30 mg/m^2 Pralatrexate 3/4 Weeks		30 mg/m^2 Pralatrexate 6/7 Weeks		45 mg/m^2 Pralatrexate 6/7 Weeks		270 mg/m^2 Pralatrexate 2/4 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	135 mg/m^2 Pralatrexate 1/2 Weeks		30 mg/m^2 Pralatrexate 3/4 Weeks		30 mg/m^2 Pralatrexate 6/7 Weeks		45 mg/m^2 Pralatrexate 6/7 Weeks		270 mg/m^2 Pralatrexate 2/4 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/16 (50%)		1/3 (33.3%)		15/27 (55.6%)		10/11 (90.9%)		10/15 (66.7%)
Blood and lymphatic system disorders
Neutropenia & Thrombocytopenia	0/16 (0%)	0	1/3 (33.3%)	1	2/27 (7.4%)	2	4/11 (36.4%)	4	2/15 (13.3%)	2
Gastrointestinal disorders
Stomatitis	6/16 (37.5%)	6	0/3 (0%)	0	3/27 (11.1%)	3	3/11 (27.3%)	3	3/15 (20%)	3
Vomitting	0/16 (0%)	0	0/3 (0%)	0	3/27 (11.1%)	3	1/11 (9.1%)	1	2/15 (13.3%)	2
Abdominal pain	0/16 (0%)	0	0/3 (0%)	0	0/27 (0%)	0	1/11 (9.1%)	1	1/15 (6.7%)	1
General disorders
General Disorders	0/16 (0%)	0	0/3 (0%)	0	6/27 (22.2%)	0	0/11 (0%)	0	1/15 (6.7%)	0
Infections and infestations
Pharyngitis	2/16 (12.5%)	2	0/3 (0%)	0	0/27 (0%)	0	1/11 (9.1%)	1	0/15 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	0/16 (0%)	0	0/3 (0%)	0	1/27 (3.7%)	1	0/11 (0%)	0	1/15 (6.7%)	1
Other (Not Including Serious) Adverse Events
	135 mg/m^2 Pralatrexate 1/2 Weeks		30 mg/m^2 Pralatrexate 3/4 Weeks		30 mg/m^2 Pralatrexate 6/7 Weeks		45 mg/m^2 Pralatrexate 6/7 Weeks		270 mg/m^2 Pralatrexate 2/4 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/16 (50%)		2/3 (66.7%)		12/27 (44.4%)		1/11 (9.1%)		5/15 (33.3%)
Gastrointestinal disorders
Nausea	8/16 (50%)	8	2/3 (66.7%)	8	12/27 (44.4%)	8	1/11 (9.1%)	8	5/15 (33.3%)	8

Limitations/Caveats

Study completed

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.